Actin disruption influences cell response upon deformation at different scales

Dr Jagoba Iturri and Professor José Luis Toca-Herrera from the Institute for Biophysics (Department of Nanobiotechnology) have studied, in collaboration with researchers from the University of Ljubljana (Slovenia), the mechanical response of endothelial cells upon treatment with cytoskeleton-disrupting drugs (CK-869 and Jasplakinolide). Mechanical properties were measured by deformation at two different ranges by means of complementary Optical Tweezers and Atomic Force Microscopy techniques.

Cytoskeleton-disrupting drugs can have different effects on cell mechanics at different deformation scales. We therefore applied two complementary indentation techniques to study the effects of two actin-disrupting drugs on cellular stiffness of Human Umbilical Vein Endothelial Cells (HUVEC). Optical tweezers were used to probe the cortical stiffness at small deformations, and atomic force microscopy (AFM) was used to probe the bulk cell stiffness at larger deformations. The first drug studied was CK-869, which is an inhibitor of actin branching complex Arp2/3, and has not been analysed yet in terms of mechanical effects. A significant decrease in cell stiffness upon treatment with CK-869 was measured with both techniques, which implies that actin branching is important for cell mechanics at small and large deformations. The second drug studied was jasplakinolide, for which ambiguous effects on cell mechanics have been reported. In line with previous studies, we found that jasplakinolide caused significant cell stiffening at large deformations but slight cell softening under small deformations. This result implies that jasplakinolide has different effects on different levels of actin organization.


Cell Stiffness under Small and Large Deformations Measured by Optical Tweezers and Atomic Force Microscopy: Effects of Actin Disruptors CK-869 and Jasplakinolide.

Authors: Spela Zemljic-Jokhadar, Jagoba Iturri, Jose Luis Toca-Herrera, Jure Derganc

Manuscript published in the Special Issue "Emerging Tools: Bioimaging of Molecules, Cell Dynamics and Mechanics" of the Journal of Physics D: Applied Physics, Dec. 2020

Full manuscript here: